Analysis of associations of polymorphic loci of the PGR gene with the development of pre-eclampsia

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INTRODUCTION

Pre-eclampsia (PE) is one of the most severe pregnancy complications that have a negative impact on the health of the pregnant woman, as well as on the condition of the fetus and newborn. PE is a multifactorial disease in the formation of which genetic factors play a significant role.

OBJECTIVE

The aim of the study was to study the associations of polymorphic loci rs484389 and rs1042838 of the PGR gene with the development of PE and to consider their regulatory potential.

MATERIAL AND METHODS

The study sample consisted of 190 pregnant women with PE and 324 women with physiological pregnancy (control group). Genotyping of polymorphic loci rs484389 and rs1042838 of the PGR gene was performed. Associations of the considered polymorphic loci with the development of PE were studied using the method of logistic regression analysis. The functional significance of the polymorphism associated with PE is considered: association with amino acid substitutions in the encoded polypeptide, association with expression (eQTL) and alternative splicing (sQTL) of genes using bioinformatic online resources (GTExportal, HaploReg, PolyPhen-2).

RESULTS

Rs1042838 polymorphism of the PGR gene is associated with the development of preeclampsia: genotype G/T (OR=1.54, 95% CI 1.02-2.33, p=0.04) and allele T (OR=1.42, 95% CI 1.01-1.98, p=0.04) increase the risk of PE, and genotype G/G (OR=0.65, 95% CI 0.43-0.97, p=0.04) and allele G (OR=0.71, 95% CI 0.49-0.99, p=0.04) have a protective value. The PGR gene rs1042838 polymorphism determines the amino acid substitution in the progesterone receptor polypeptide (Val660Leu), is associated with the expression of the PGR gene in fibroblast cell culture, subcutaneous adipose tissue, and adrenal glands, affects the level of alternative splicing of the PGR-AS1 transcript in the ovaries, and determines the affinity of DNA to four transcription factors (AP-2rep, BDP1_disc3, cacd_1, SP4), is located in the region of modified histones that mark enhancers and promoters in the culture of mesoderm cells, trophoblast derivatives, and ovaries.

CONCLUSIONS

The rs1042838 polymorphism of the PGR gene is associated with the development of pre-eclampsia.

Keywords:

pre-eclampsia

single-nucleotide polymorphism

PGR

associations

Authors:

Golovchenko O.V.

Belgorod State National Research University

Abramova M.Yu.

Belgorod State National Research University

ORCID: 0000-0002-1406-2515

Ponomarenko I.V.

Belgorod State National Research University

ORCID: 0000-0002-5652-0166

Churnosov M.I.

Belgorod State National Research University

ORCID: 0000-0003-1254-6134

Received:

11.11.2020

Accepted:

12.12.2020

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